Natural Product Vibsanin A Induces Differentiation of Myeloid Leukemia Cells through PKC Activation.

All-trans retinoic acid (ATRA)-based cell differentiation therapy has been successful in treating acute promyelocytic leukemia, a unique subtype of acute myeloid leukemia (AML). However, other subtypes of AML display resistance to ATRA-based treatment. In this study, we screened natural, plant-derived vibsane-type diterpenoids for their ability to induce differentiation of myeloid leukemia cells, discovering that vibsanin A potently induced differentiation of AML cell lines and primary blasts. The differentiation-inducing activity of vibsanin A was mediated through direct interaction with and activation of protein kinase C (PKC). Consistent with these findings, pharmacological blockade of PKC activity suppressed vibsanin A-induced differentiation. Mechanistically, vibsanin A-mediated activation of PKC led to induction of the ERK pathway and decreased c-Myc expression. In mouse xenograft models of AML, vibsanin A administration prolonged host survival and inhibited PKC-mediated inflammatory responses correlated with promotion of skin tumors in mice. Collectively, our results offer a preclinical proof of concept for vibsanin A as a myeloid differentiation-inducing compound, with potential application as an antileukemic agent. Cancer Res; 76(9); 2698-709. ©2016 AACR.

Two new phenylpropanoids from Micromelum integerrimum.

AIM: To investigate the chemical and bioactive constituents from the stems and leaves of Micromelum integerrimum. METHOD: The chemical constituents were isolated and purified by silica gel, Sephadex LH-20, and HPLC. Their structures were mainly elucidated on the basis of extensive 1D- and 2D-NMR spectroscopy and mass spectrometry. Their cytotoxicity and antimicrobial activities were tested by the SRB and turbidimetric methods, respectively. RESULTS: Two new phenylpropanoids and two known coumarins were obtained, and their structures were identified as microintegerrin A (1), microintegerrin B (2), scopoletin (3), and scopolin (4). All of the compounds were tested for their cytotoxicity against three cancer cell lines (HeLa, A549, and BGC-823) and for antimicrobial activity against the fungus Candida albicans and the bacterium Staphylococcus aureus. CONCLUSION: Two new phenylpropanoids 1 and 2 were isolated and identified from the stems and leaves of M. intgerrimum. None of the compounds showed cytotoxic or antimicrobial activity at the tested concentration of 20 µg·mL(-1).

Astershionones A-F, six new anti-HBV shionane-type triterpenes from Aster tataricus.

Six new shionane-type triterpenes, astershionones A-F (1-6), were obtained from the roots and rhizomes of Aster tataricus. Their structures were elucidated on the basis of spectroscopic data, mainly NMR and MS data. The absolute configuration of 1 was determined by single crystal X-ray diffraction analysis and CD analysis. 3 showed inhibitory activity against HBsAg and HBeAg secretion with IC50 values of 23.0 and 23.1 µM, and cytotoxicity against HepG 2.2.15 cells with a CC50 value of 170.5 µM. 3 also exhibited inhibitory activity against HBV DNA replication with an IC50 value of 22.4 µM.

Astataricusones A-D and astataricusol A, five new anti-HBV shionane-type triterpenes from Aster tataricus L. f.

Five new shionane-type triterpenes, astataricusones A-D (compounds 1-4) and astataricusol A (5), together with one known shionane-type triterpene 6 were obtained from the roots and rhizomes of Aster tataricus L. f. Their structures were elucidated on the basis of spectroscopic data, mainly NMR and MS data. The absolute configurations of 1 and 4 was determined by single crystal X-ray diffraction and CD analysis. Compound 2 showed inhibitory activity on HBsAg secretion with an IC50 value of 23.5 µM, while 2 and 6 showed inhibitory activities on HBeAg secretion with IC50 values of 18.6 and 40.5 µM, and cytotoxicity on HepG 2.2.15 cells with CC50 values of 172.4 and 137.7 µM, respectively. Compounds 2 and 6 also exhibited inhibitory activities on HBV DNA replication with IC50 values of 2.7 and 30.7 µM, respectively.

[Effects of Salviae miltiorrhizae and Platycodon grandiflorum in Tianwang Buxin decoction for microcirculation of brain meninx vascullosa in rats].

OBJECTIVE: To investigat the effects of Salviae miltiorrhizae and Platycodon grandiflorum in Tianwang Buxin decoction for microcirculation of brain meninx vascullosa in rats. METHOD: The rats were equally and randomly divided into six groups. Control, Tianwang Buxin decoction, P. grandiflorum-absenced Tianwang Buxin decoction, Radix S. miltiorrhizae, Radix S. miltiorrhizae and P. grandiflorum, P. grandiflorum. The effect on brain meninx vascullosa in rats were observed through an inverted microscope, doppler perfusion imager and blood reheology measurement meter. RESULT: The effect of Tianwang Buxin decoction was best among the six groups in dilatation of the diameter of arterial and venule, and velocity of blood flow. The effect of Radix Salviae miltiorrhizae was postponed and decreased when P. grandflorum was removed of from this prescription. However, it was minimal advance of blood apparent-viscosity for Tianwang Buxin decoction. CONCLUSION: It is indeed that P. grandiflorum leads S. miltiorrhizae to main and collaterall channel, goes up like the boat and oar and aims to reinforce affection for the other drugs of Tianwang Buxin decoction to mprove the microcirculation of brain meninx vascullosa of rats.